A Novel Postbiotic From Lactobacillus rhamnosus GG With a Beneficial Effect on Intestinal Barrier Function

Abstract

It has long been known that probiotics can be used to maintain intestinal homeostasis and treat a number of gastrointestinal disorders, but the underlying mechanism has remained obscure. Recently, increasing evidence supports the notion that certain probiotic-derived components, such as bacteriocins, lipoteichoic acids, surface layer protein and secreted protein, have a similar protective role on intestinal barrier function as that of live probiotics. These bioactive components have been named ‘postbiotics’ in the most recent publications. We previously found that the Lactobacillus rhamnosus GG (LGG) culture supernatant is able to accelerate the maturation of neonatal intestinal defense and prevent neonatal rats from oral Escherichia coli K1 infection. However, the identity of the bioactive constituents has not yet been determined. In this study, using liquid chromatography-tandem mass spectrometry analysis, we identified a novel secreted protein (named HM0539 here) involved in the beneficial effect of LGG culture supernatant. HM0539 was recombinated, purified, and applied for exploring its potential bioactivity in vitro and in vivo. Our results showed that HM0539 exhibits a potent protective effect on the intestinal barrier, as reflected by enhancing intestinal mucin expression and preventing against lipopolysaccharide (LPS)- or tumor necrosis factor α (TNF-α)-induced intestinal barrier injury, including downregulation of intestinal mucin (MUC2), zonula occludens-1 (ZO-1) and disruption of the intestinal integrity. Using a neonatal rat model of E. coli K1 infection via the oral route, we verified that HM0539 is sufficient to promote development of neonatal intestinal defense and prevent against E. coli K1 pathogenesis. Moreover, we further extended the role of HM0539 and found it has potential to prevent dextran sulfate sodium (DSS)-induced colitis as well as LPS/D-galactosamine-induced bacterial translocation and liver injury. In conclusion, we identified a novel LGG postbiotic HM0539 which exerts a protective effect on intestinal barrier function. Our findings indicated that HM0539 has potential to become a useful agent for prevention and treatment of intestinal barrier dysfunction- related diseases.

The gut-liver axis in liver disease: Pathophysiological basis for therapy

“…p40 molecule, HM0539), enzymes, peptides, bacteriocins, endo-and exo-polysaccharides, vitamins and organic acids. 159 In general, postbiotic components have been reported to possess immunomodulatory and protective roles on intestinal barrier function. In particular, postbiotics can act on immune cells protecting the gut tissue from immunopathology by increasing the secretion of anti-inflammatory cytokines such as IL-10.…”

Molecules Produced by Probiotics and Intestinal Microorganisms with Immunomodulatory Activity

“…Besides, two secreted proteins from lactobacilli, p75 and p40, have been found capable of inhibiting cell apoptosis induced by proinflammatory states [13]. A novel secreted protein from L. rhamnosus GG, HM0539, has been deemed as being responsible for the protective effects exhibited by the corresponding producing strain on the intestinal barrier, enhancing intestinal mucin expression and preventing lipopolysaccharide (LPS) or TNFα-induced intestinal barrier injury [14].…”

Influence of natural dairy probiotics on health

“…These metabolites prevent intestinal motor disorders resulting from bacterial infection [58]. Gao et al showed that protein HM0539 produced by L. rhamnosus GG protects the intestinal microbiome and its activity increasing mucin secretion, reducing intestinal permeability, and promoting the expression of proteins forming tight intestinal connections [59]. They also examined the effect of HM0539 on two diseasescolitis and acute hepatic failure.…”

“…They also examined the effect of HM0539 on two diseasescolitis and acute hepatic failure. In both cases, the use of this protein had a protective effect on the function of the intestinal barrier and alleviating the course of these diseases [59]. In addition, Han et al have shown the preventive effect of L. rhamnosus GG protein metabolites against intestinal microbiom disorders caused by interferon-γ in patients with IBS (irritable bowel syndrome) [60].…”